Systemic neutralizing antibodies induced by long interval mucosally primed systemically boosted immunization correlate with protection from mucosal SHIV challenge.
Immune correlates of vaccine protection from HIV-1 infection would provide important milestones to guide HIV-1 vaccine development. In a proof of concept study using mucosal priming and systemic boosting, the titer of neutralizing antibodies in sera was found to correlate with protection of mucosally exposed rhesus macaques from SHIV infection. Mucosal priming consisted of two sequential immunizations at 12-week intervals with replicating host range mutants of adenovirus type 5 (Ad5hr) expressing the HIV-1(89.6p) env gene. Following boosting with either heterologous recombinant protein or alphavirus replicons at 12-week intervals animals were intrarectally exposed to infectious doses of the CCR5 tropic SHIV(SF162p4). Heterologous mucosal prime systemic boost immunization elicited neutralizing antibodies (Nabs), antibody-dependent cytotoxicity (ADCC), and specific patterns of antibody binding to envelope peptides. Vaccine induced protection did not correlate with the type of boost nor T-cell responses, but rather with the Nab titer prior to exposure.
Bogers
Willy M J M
WM
Department of Virology, Biomedical Primate Research Centre (BPRC), P.O. Box 3306, 2280 GH Rijswijk, The Netherlands. bogers@bprc.nl
Davis
David
D
Baak
Ilona
I
Kan
Elaine
E
Hofman
Sam
S
Sun
Yide
Y
Mortier
Daniella
D
Lian
Ying
Y
Oostermeijer
Herman
H
Fagrouch
Zahra
Z
Dubbes
Rob
R
van der Maas
Martin
M
Mooij
Petra
P
Koopman
Gerrit
G
Verschoor
Ernst
E
Langedijk
Johannes P M
JP
Zhao
Jun
J
Brocca-Cofano
Egidio
E
Robert-Guroff
Marjorie
M
Srivastava
Indresh
I
Barnett
Susan
S
Heeney
Jonathan L
JL
D016915:AIDS Vaccines / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D015752:Genes, env; D015483:HIV Antibodies / Q000096:biosynthesis*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008253:Macaca mulatta; D008297:Male; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000008:administration & dosage*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004279:DNA, Viral; D015483:HIV Antibodies; D018449:SAIDS Vaccines